Effects of Phentolamine on Responses to PAMP in the Hindquarters Vascular Bed of the Rat.

Abstract

BACKGROUND: Responses to proadrenomedullin NH(2)-terminal 20 peptide (PAMP), a novel hypotensive peptide formed from preproadrenomedullin, and the effects of inhibition of adrenergic vasomotor tone with the alpha-receptor antagonist, phenolamine, on responses to PAMP were investigated in the systemic and hindquarters vascular bed of the rat. METHODS AND RESULTS: Intravenous injections of PAMP decreased systemic arterial pressure and in the hindquarters vascular bed of the rat under conditions of controlled hindquarters blood flow, intra-arterial injections of PAMP decreased perfusion pressure in a dose-related manner. Following administration of the alpha receptor blocking agent, phenotlamine, systemic depressor and hindquarters vasodilator responses to PAMP were not significantly decreased, whereas phentolamine significantly decreased systemic and hindquarters pressor responses to norepinephrine. Phentolamine had no significant effect on vasodilator responses to bradykinin, albuterol, or to nitroglycerin. CONCLUSIONS: The present data show that PAMP has significant systemic vasodepressor and vasodilator activity in the hindquarters vascular bed of the rat and suggest that vasodepressor and hindquarters vasodilator responses to PAMP are not dependent upon the presence of adrenergic vasomotor tone.